BackgroundPeutz-Jeghers syndrome PJS is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11-LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11-LKB1 and their association to disease phenotype.

MethodsMutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification MLPA. Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations.

ResultsThirteen different pathogenic mutations in STK11, including a high frequency of large genomic deletions 38%, 5-13, were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes SBNO2 and GPX4, located upstream of STK11, with a possible modifier effect. The majority of the point mutations 88%, 7-8 can be considered novel. Quantification of the STK11 transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3.

ConclusionsA combination of sensitive techniques may assure a high 100% STK11 mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-11-169 contains supplementary material, which is available to authorized users.